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Biomedical subjects

R A deLemos

Publications and source records attributed to R A deLemos.

At least 55 records · Page 3Linked to original sources

Diffuse alveolar damage in the evolution of bronchopulmonary dysplasia in the baboon.

Pulmonary immaturity, oxygen exposure that elicits cellular damage by free radicals, and barotrauma induced by mechanical ventilation are implicated in the pathogenesis of bronchopulmonary dysplasia. In the adult counterpart of adult respiratory distress syndrome, diffuse alveolar damage characterizes a histopathological sequence of lung findings that can occur during the disease course. Although adult respiratory distress syndrome has many etiologies, elevated oxygen exposure is known to be a contributor to the ensuing lung injury. In bronchopulmonary dysplasia, oxygen exposure is thought to be a primary agent of injury. The evolution of the histopathological findings in the premature baboon model of hyaline membrane disease/bronchopulmonary dysplasia was investigated in this study and compared to that in oxygen-treated adult baboons with adult respiratory distress syndrome. Findings from lung specimens of 121 prematurely delivered baboons at 0, 0.5, 1, 2, 3-6, 7-11+ days after delivery document that the premature lung has a delayed and more blunted exudative response when compared to that of human and baboon adults. Saccular edema, not hyaline membranes, is the dominant histopathological finding in the exudative phase of diffuse alveolar damage and occurs later (7-11 days) in infant lungs when compared to comparably treated adult lungs in which maximal exudative changes are seen at 3-6 days. The reparative response in the premature baboon is characterized by saccular wall thickening and fibrosis, with less intramural organization of exudate in saccular/alveolar spaces when compared to adults. The airway changes in the premature are more severe than those seen in adult disease. These findings indicate that diffuse alveolar damage does occur in the immature lung albeit with differing characteristics when contrasted to comparably injured adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High-frequency ventilation: its various techniques and clinical applications.

High-frequency ventilation can be considered to be ventilation with a tidal volume close to or less than the anatomical dead space. The various techniques of high-frequency ventilation will be discussed including high-frequency positive pressure ventilation, high-frequency jet ventilation or high-frequency flow interruption, and high-frequency oscillatory ventilation. The clinical application of the various types of high-frequency ventilation will be discussed including their use during surgical procedures, their use for various kinds of barotrauma, their usefulness in respiratory failure, their use in newborns with hyaline membrane disease, and their usefulness for respiratory support in emergency situations involving cardiopulmonary resuscitation. The potential use for high-frequency ventilation in the management of battlefield casualties and air evacuation of critically ill patients will also be discussed.

Barotrauma↗

Tracheal and bronchial injury in high-frequency oscillatory ventilation compared with conventional positive pressure ventilation.

We compared airway histopathologic findings in premature baboons given standard positive pressure ventilation with those seen after high-frequency oscillatory ventilation. Six animals received standard frequency conventional ventilation for a mean of 9.2 days; seven received high-frequency oscillatory ventilation at 10 Hz using a piston oscillator for a mean of 10.2 days; five baboons served as controls, and were killed immediately after birth. A semiquantitative histopathologic scoring system was used to grade tissue changes in the trachea, carina, and both mainstem bronchi. Compared with the nonventilated control animals, injury was produced with both forms of mechanical ventilation (P less than 0.01 for both instruments); however, the degree of damage was mild, with no significant difference in the extent of injury between the two treatment groups. High-frequency oscillatory ventilation appears to result in no greater degree of airway damage than conventional positive pressure ventilation.

Animals↗

Extracorporeal membrane oxygenation and high-frequency oscillatory ventilation: potential therapeutic relationships.

Eighteen neonates 33 to 42 wk gestational age with severe respiratory failure were referred for extracorporeal membrane oxygenation (ECMO). Sixteen ultimately met the ECMO criteria, of whom 15 were first offered high-frequency oscillatory ventilation (HFOV). Seven responded to HFOV alone and did not require ECMO treatment. Eight of the nine remaining patients were placed on ECMO support with HOFV. Infants who responded to HFOV alone tended to have pneumonia more than meconium aspiration, to be smaller and more immature, to have higher Apgar scores, and to have suffered severe hypoxia (alveolar-arterial oxygen pressure difference over 600 torr) for less time than the ECMO group. Although patient numbers are small, a trend is noted which favors HFOV treatment alone in terms of the duration of HFOV, the total duration of assisted ventilation, the rapidity with which extubation was accomplished, and the length of hospital stay.

Birth Weight↗

Animal models for evaluation of drugs for use in the mature and immature newborn.

The need for a better defined and controlled approach to new therapies for possible neonatal application appears clear in light of present practice and recent history. At this conference several animal models were discussed that could be used for pharmacokinetic and pharmacodynamic studies and for evaluation of efficacy and safety prior to human newborn testing. This, coupled with a requirement for comprehensive human data collection following preliminary approval of new drugs, would, we believe, significantly improve present practice. It will, however, require pressure from the medical community and patient advocates to encourage change in current government regulations and industry policies.

Animals↗

A nonpulmonary complication of high-frequency oscillation.

High-frequency ventilation (HFV) has been suggested as an alternative to standard positive-pressure ventilation with positive end-expiratory pressure (PPV/PEEP) in the treatment of infants with hyaline membrane disease. To assess the relative safety and efficacy of HFV, we compared standard PPV to HFV delivered by oscillation (HFO) and HFV delivered by a flow interrupter (HFFI) in a previously validated preterm baboon model of hyaline membrane disease. At necropsy, the livers of several animals were unexpectedly found to have severe fatty change and/or cytoplasmic vacuolization and edema. There was a strong correlation between use of HFO and the development of liver lesions. The hepatic lesion may reflect decreased cardiac output with a concomitant fall in splenic perfusion and/or alterations in normal intrathoracic pressure that increase resistance in the hepatic vasculature. Although the etiology cannot be determined precisely, these data suggest the potential for nonpulmonary complications of HFV in the immature newborn and mandate further investigation before its widespread clinical application.

Animals↗

Differential pulmonary auscultation in neonates.

Auscultation of neonates by means of conventional techniques is subject to many errors. Consequently, pediatricians rely on radiographs for much of their information regarding ventilation abnormalities. We report a method of simultaneous differential auscultation, using a double-headed stethoscope, which allows better auscultatory evaluation of neonates. The technique is simple and easily learned. The equipment used is inexpensive and easily constructed. The technique is most useful in emergency and transport situations when radiographs are not readily available.

Auscultation↗

Subgaleal hemorrhage in a premature infant with congenital diaphragmatic hernia following vacuum-assisted delivery.

An infant with congenital diaphragmatic hernia was delivered by vacuum extraction, with a resultant subgaleal hemorrhage that excluded him from ECMO. The literature regarding vacuum-assisted delivery and birth trauma is reviewed in the context of congenital anomalies that may require ECMO support, and recommendations for perinatal management are suggested.

Adult↗

Low serum cortisol in term newborns with refractory hypotension.

OBJECTIVES: The aim of this study is to measure baseline serum cortisol levels and clinical response to glucocorticoid therapy in a group of term infants with refractory hypotension. STUDY DESIGN: Seven term newborns with refractory hypotension were included. Serum cortisol levels were drawn before initiation of glucocorticoid therapy and measured by either fluorescence polarization immunoassay or radioimmunoassay. Baseline blood pressures, heart rate, and inotropes doses were recorded at baseline, then 4, 8, 12, 24, 48, 72, and 96 hours after glucocorticoid therapy. Urine output and volume expanders the infants received were recorded 24 hours before and after glucocorticoid therapy. Dexamethasone was used at a starting dose of 0.2 mg/kg per day divided every 12 hours. The statistical analysis was done using analysis of variance with repeated measures and paired t-test. RESULTS: Serum cortisol levels of the infants ranged from 2.0 to 15.4 micrograms/dl. After initiation of glucocorticoid therapy, there was significant improvement of blood pressure. Vasopressors were rapidly weaned and discontinued within 72 hours. In three of seven infants, no volume expanders were required after initiation of steroids, and none needed volume expanders after 2 days. Urine output increased significantly within 24 hours. All infants survived. CONCLUSIONS: Glucocorticoids improved pressure and stabilized clinical conditions of a group of term newborns with refractory hypotension. Serum cortisol levels of these infants were relatively low. We speculate that a subset of critically ill term infants has relative adrenal insufficiency and glucocorticoid therapy may be essential.

Blood Pressure↗

High frequency ventilation--the relationship between ventilator design and clinical strategy in the treatment of hyaline membrane disease and its complications: a brief review.

Progress in the application of techniques of HFV to clinical settings has been hampered by a lack of comparative data. Ventilator design and/or strategy place clear limitations on the effective and safe use of these devices. There is a definite need to develop clear therapeutic goals for HFV, to define the operating characteristics and limitations of each device, and to develop effective and safe strategies for their use in various clinical settings. Only then can adequate controlled clinical trials be performed and the role of these techniques be firmly established.

Cardiac Output↗

Severe retinopathy of prematurity in extremely low birth weight infants after short-term dexamethasone therapy.

With advances in neonatal intensive care survival of extremely low birth weight (< 1 kg) infants has increased significantly over the past decade. Dexamethasone is used increasingly for the prevention and treatment of chronic lung disease in these infants. The impact of dexamethasone therapy on the incidence or severity of retinopathy of prematurity (ROP) remains controversial. We conducted a retrospective study to evaluate the association between short-term dexamethasone treatment and severe ROP in extremely low birth weight infants. From October 1989 to December 1992, 309 very low birth weight infants were admitted to the neonatal intensive care unit. A total of 266 infants (86%) survived until hospital discharge. Of these, 90 weighed less than 1 kg. Thirty-eight of 90 infants received short-term dexamethasone therapy for chronic lung disease and the remaining 52 infants did not. Infants treated with dexamethasone and those not treated with dexamethasone were comparable in birth weight (820 vs 828 gm), gestational age (26.5 vs 26.9 weeks), inborn (11 vs 14), and occurrence of sepsis (13/38 vs 21/52). Infants treated with dexamethasone required longer periods of mechanical ventilation (44 +/- 23 vs 26 +/- 15 days, p < 0.001), had longer duration of supplemental oxygen (57 +/- 28 vs 29 +/- 23 days, p < 0.001), had higher incidence of patent ductus arteriosus (28/38 vs 18/52, p < 0.0003), and required surfactant therapy more often for respiratory distress syndrome (17/38 vs 11/52, p < 0.01), when compared with infants who did not receive dexamethasone. Severe ROP developed in 16 infants (stage III or higher); 12 of these were in the dexamethasone-treated group (p < 0.003). Thirteen infants required cryotherapy; nine were from the dexamethasone-treated group (p < 0.13). This study demonstrates an apparent association between the incidence of severe ROP and dexamethasone therapy. Prospective, randomized, controlled studies are needed to correct for differences in severity of cardiorespiratory illness to establish whether a causal role exists for steroid therapy in ROP. Until such studies are available, careful consideration must be given to indications, dosage, time of initiation, and duration of treatment with dexamethasone in extremely low birth weight infants.

Case-Control Studies↗